The ultimate goal of this project is to develop a rational treatment program for urolithiasis, in which the treatment is selected on the basis of its appropriate physicochemical effects on stone formation in urine, the correction of underlying physiologic derangements, and minimum potential complications. This goal will be pursued by four multidisciplinary approaches, representing separate components of this SCOR proposal. In the first component (Biochemical and Physicochemical), studies will be concerned with the characterization of promoters and inhibitors of crystallization in urine and in stones. The second component (Physiological) will consider the mode of intestinal absorption of stoneforming substances using triple-lumen technique, role of vitamin D in urolithiasis, and the pathophysiology of hypercalciurias. The third component will be concerned with the analysis of the mode of action of various modalities for urolithiasis, including allopurinol, diphenylhydantoin and magnesium cellulose phosphate. Both physicochemical and physiological action of modalities will be sought. The final component will address the important problem of diagnosis and therapy of nephrolithiasis. A reliable ambulatory protocol for the diagnosis of various causes of stones will be developed. Working criteria for optimum therapy will be formulated whereby a specific treatment is chosen for a particular cause of stones, on the basis of its ability to "correct" physicochemical and physiological derangements. The rational therapy of urolithiasis will have been achieved if during long-term clinical trials, the particular optimum therapy is shown to prevent stone formation, exert appropriate physicochemical effects in urine, correct underlying physiologic disorders and cause minimal or tolerable side-effects.